The present disclosure relates generally to controlled release therapeutic objects, and more particularly to such objects formed from porous materials having immobilized encapsulated biomolecules.
Various accidents and diseases result in severe tissue loss and organ failures. For example, in dentistry, periodontal disease afflicts over 50% of the adult population in the United States, with approximately 10% displaying severe disease concomitant with early tooth loss. This disease is often marked by destruction of periodontal support (i.e., periodontal ligament (PDL), cementum and bone). The recognition that periodontal regeneration can be achieved, including formation of new bone, new cementum and supportive PDL, has resulted in increased attempts to develop regenerative therapies.
Bone morphogenetic proteins (BMPs) are suitable for use in bone development and regeneration. Such proteins have been demonstrated to elicit new bone formation both at orthotopic and ectopic sites in experimental animal models. Recombinant BMPs are believed to hold great promise for healing bone fractures, bridging bone nonunions, preventing osteoporosis, and treating periodontal defects.
While BMPs have great potential, exogenous administration of BMPs in a buffer solution does not insure satisfactory new bone induction, especially in higher mammals. The rapid diffusion of BMPs away from application site and the loss of bioactivity leads, in some instances, to insufficient local induction, incomplete bone regeneration, or failure of bone regeneration.
Delivery of BMPs from collagen matrices has been successful in preclinical and human clinical trials; however, disadvantages are still present. Using this technique, it may be difficult to retain the BMPs formulated in a collagen matrix for a sufficient duration, which may result in greater loading and response variability in vivo. In addition, the biodegradability and three-dimensional structures of a collagen matrix are difficult to control. Since BMPs are physically entrapped within collagen, the capability of control over release kinetics from the collagen matrix may be limited. As such, collagen may not be appropriate for applications where varying release rate is desirable. Issues in terms of immunogenicity and disease transmission may also be of concern when using collagen.
Another of the existing regenerative therapies is the use of grafting materials. Grafting materials include autografts (tissues from the same individual), allografts (tissues from human cadavers and bone banks), xenografts (tissues from a different species), and alloplasts (“inert” synthetic materials). Major concerns regarding the use of autografts are the potentially inadequate size and shape. Major concerns regarding the use of allografts and xenografts are the risk of long-term foreign body reaction, limited new bone formation, limited gain of clinical attachment level, the risk of pathogen transmission and immune rejection, and combinations thereof.
Guided-tissue-regeneration (GTR) membranes have also been used either alone or in combination with graft materials. The principle of GTR is to provide an environment that allows the appropriate cells (i.e., those that can enhance formation of periodontal tissues) to repopulate the wound site while excluding cells that may impair periodontal wound healing (e.g., epithelial cells). This is accomplished by placing a barrier over the periodontal defect, thereby preventing cells from the surrounding gingival and epithelium tissues from migrating into the defective sites, and allowing the desired cells (such as PDL fibroblasts, cementoblasts, osteoblasts, or their progenitor cells) to populate the sites. Although significant restoration may be achieved with GTR therapy, with or without the use of graft materials, results are not predictable, and complete regeneration of periodontal defects may not be achieved. This may likely be due to the inherent limitations in the GTR approach, which, in part, relies passively on the natural wound healing process.